gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

Significance of different CD133 phenotypes in glioblastoma

Meeting Abstract

  • C. Herold-Mende - Sektion Neurochirurgische Forschung, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • B. Campos - Sektion Neurochirurgische Forschung, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • L. Zeng - Sektion Neurochirurgische Forschung, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • P. DaoTrong - Sektion Neurochirurgische Forschung, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • H. Mairbäurl - Innere Medizin VII, Universitätsklinikum Heidelberg, Heidelberg
  • A. Unterberg - Sektion Neurochirurgische Forschung, Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.07.01

DOI: 10.3205/11dgnc038, URN: urn:nbn:de:0183-11dgnc0380

Veröffentlicht: 28. April 2011

© 2011 Herold-Mende et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: The biological significance of CD133 in glioblastoma has been the subject of controversial scientific debate. Above all, there is disagreement concerning the proper approach, the appropriate (cell) model and the suitable microenvironment to study this molecule, which often led to inconsistent experimental results among studies.

Methods: In consideration of a primary need to dissect and to understand the CD133 phenotype in glioblastoma, we performed a comprehensive analysis of CD133 expression and its regulation in a large set of different glioblastoma cell lines (n=20) by qPCR, FACS analysis and immunocytochemistry. Our analysis considered alternatively spliced mRNA transcripts, different protein epitopes as well as varying sub-cellular localizations of CD133 and explored its regulation under pertinent microenvironmental conditions such as normoxia and hypoxia.

Results: In our study sample, CD133 mRNA and the CD133 protein could be detected in all relevant types of cell lines, regardless of the experimental context and without qualitative differences. Corresponding to the prevalence of CD133 mRNA we detected intracellular CD133 protein accumulations, which were either located to the ER, the golgi apparatus or both but were unrelated to particular CD133 mRNA splice variants or individual protein epitopes. In contrast, extracellular membrane-bound expression of CD133 was restricted to tumor cells bearing the extracellular CD133 epitope AC133. In the latter, differentiation-permissive culture conditions and physiological oxygen levels clearly influenced AC133 expression, CD133 mRNA levels and CD133 protein expression. In addition, we demonstrate that modulation of AC133 expression levels in AC133-positive tumor cells occurs independent of changes in CD133 mRNA transcription, CD133 protein translation, protein retention or protein shedding. We propose that this might be due to discrete changes in the extracellular CD133 protein resulting in either exposure or masking of the AC133 epitope.

Conclusions: Our results corroborate an important role for the AC133 epitope because neither CD133 mRNA nor protein content but only AC133 levels mirror cellular changes that occur under malignancy-modulating conditions such as differentiation and reduced oxygen levels.